Small Nucleolar RNAs (snoRNAs) are non-coding RNAs involved in RNA processing (1). There are two major subclasses of snoRNAs, termed box C/D and box H/ACA snoRNAs. These two classes contain guide sequences that are known to canonically pair with complementary regions on a target pre-rRNA, forming a RNA duplex and facilitating the enzymatic activity of methylases and uridylases that site specifically modify pre-rRNA bases by either 2′-O-methylation or pseudouridylation respectively. These modifications of the rRNA are critical to ribosome assembly and viability. In the last decade, various orphan snoRNAs have been identified that structurally resemble C/D box snoRNAs but do not contain sequence complementarity to rRNA. While some snoRNAs and other non-coding RNAs have been implicated in diseases or other disorders, there remains an ongoing need to identify, characterize and develop compositions and methods which harness the involvement of snoRNAs for diagnosis and therapy of such diseases and disorders.